De Novo design of potential inhibitors against SARS-CoV-2 Mpro.

The impact of the ravages of COVID-19 on people's lives is obvious, and the development of novel potential inhibitors against SARS-CoV-2 main protease (Mpro), which has been validated as a potential target for drug design, is urgently needed. This study developed a model named MproI-GEN, which can be used for the de novo design of potential Mpro inhibitors (MproIs) based on deep learning. The model was mainly composed of long-short term memory modules, and the last layer was re-trained with transfer learning. The validity (0.9248), novelty (0.9668), and uniqueness (0.0652) of the designed potential MproI library (PMproIL) were evaluated, and the results showed that MproI-GEN could be used to design structurally novel and reasonable molecules. Additionally, PMproIL was filtered based on machine learning models and molecular docking. After filtering, the potential MproIs were verified with molecular dynamics simulations to evaluate the binding stability levels of these MproIs and SARS-CoV-2 Mpro, thereby illustrating the inhibitory effects of the potential MproIs against Mpro. Two potential MproIs were proposed in this study. This study provides not only new possibilities for the development of COVID-19 drugs but also a complete pipeline for the discovery of novel lead compounds.

A proposed artificial intelligence workflow to address application challenges leveraged on algorithm uncertainty.

Artificial Intelligence (AI) has achieved state-of-the-art performance in medical imaging. However, most algorithms focused exclusively on improving the accuracy of classification while neglecting the major challenges in a real-world application. The opacity of algorithms prevents users from knowing when the algorithms might fail. And the natural gap between training datasets and the in-reality data may lead to unexpected AI system malfunction. Knowing the underlying uncertainty is essential for improving system reliability. Therefore, we developed a COVID-19 AI system, utilizing a Bayesian neural network to calculate uncertainties in classification and reliability intervals of datasets. Validated with four multi-region datasets simulating different scenarios, our approach was proved to be effective to suggest the system failing possibility and give the decision power to human experts in time. Leveraging on the complementary strengths of AI and health professionals, our present method has the potential to improve the practicability of AI systems in clinical application.

Distinct Disease Severity Between Children and Older Adults With Coronavirus Disease 2019 (COVID-19): Impacts of ACE2 Expression, Distribution, and Lung Progenitor Cells.

BACKGROUND: Children and older adults with coronavirus disease 2019 (COVID-19) display a distinct spectrum of disease severity yet the risk factors aren't well understood. We sought to examine the expression pattern of angiotensin-converting enzyme 2 (ACE2), the cell-entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and the role of lung progenitor cells in children and older patients. METHODS: We retrospectively analyzed clinical features in a cohort of 299 patients with COVID-19. The expression and distribution of ACE2 and lung progenitor cells were systematically examined using a combination of public single-cell RNA-seq data sets, lung biopsies, and ex vivo infection of lung tissues with SARS-CoV-2 pseudovirus in children and older adults. We also followed up patients who had recovered from COVID-19. RESULTS: Compared with children, older patients (>50 years.) were more likely to develop into serious pneumonia with reduced lymphocytes and aberrant inflammatory response (P = .001). The expression level of ACE2 and lung progenitor cell markers were generally decreased in older patients. Notably, ACE2 positive cells were mainly distributed in the alveolar region, including SFTPC positive cells, but rarely in airway regions in the older adults (P < .01). The follow-up of discharged patients revealed a prolonged recovery from pneumonia in the older (P < .025). CONCLUSIONS: Compared to children, ACE2 positive cells are generally decreased in older adults and mainly presented in the lower pulmonary tract. The lung progenitor cells are also decreased. These risk factors may impact disease severity and recovery from pneumonia caused by SARS-Cov-2 infection in older patients.

Depressive State in the Emergency Department During COVID-19: A National Cross-Sectional Survey in China.

Chinese emergency department (ED) staff encountered significant mental stress while fighting the coronavirus disease 2019 (COVID-19) pandemic. We sought to investigate the prevalence and associated factors for depressive symptoms among ED staff (including physicians, nurses, allied health, and auxiliary ED staff). A cross-sectional national survey of ED staff who were on duty and participated in combating the COVID-19 pandemic was conducted March 1-15, 2020. A total of 6,588 emergency medical personnel from 1,060 hospitals responded to this survey. A majority of respondents scored above 10 points on the PHQ-9 standardized test, which is associated with depressive symptoms. Those aged 31-45, those working in the COVID-19 isolation unit, and those with relatives ≤ 16 or ≥70 years old at home all had statistically significant associations with scoring >10 points. Depressive symptoms among Chinese emergency medical staff were likely quite common during the response to the COVID-19 pandemic and reinforce the importance of targeted ED staff support during future outbreaks.

Clinical outcomes of pleural drainage on pneumothorax and hydrothorax in critically ill patients with COVID-19: A case series with literature review.

BACKGROUND: For patients with COVID-19, pneumothorax and hydrothorax are suggested to be negative prognostic indicators. However, the management of these two conditions has rarely been discussed. We aimed to describe the clinical outcomes of pleural drainage in critically ill patients with COVID-19. METHODS: A total of 17 pleural drainages were performed in 11 critically ill patients with pneumothorax or hydrothorax. Either chest tubes or central venous catheters (CVCs) were used. The clinical outcomes, including respiratory and circulation indicators at 24 h and 1 h before the procedure and 24 h and 48 h after the procedure, were retrospectively recorded. RESULTS: (1) Following pleural drainage, there was a 19.1% improvement in the PaO2/FiO2 ratio from 147.4 mmHg (-1 h) to 175.5 mmHg (24 h), while the mean positive end expiratory pressure (PEEP) decreased from 10.7 cmH2O (-1 h) to 8.9 cmH2O (24 h) and 8.1 cmH2O (48 h). The A-a gradients decreased from 313.3 mmHg (-1 h) to 261.3 mmHg (24 h). (2) The dosage of norepinephrine increased from 0.15 µg/kg/min (-1 h) to 0.40 µg/kg/min (24 h). (3) No haemorrhagic or infectious complications were observed. (4) A total of 41.6% of CVCs were partially or fully obstructed, while no chest tubes were obstructed. CONCLUSION: For critically ill patients with COVID-19, pleural drainage leads to a significant improvement in oxygenation and gas exchange, but the deterioration of circulation is not reversed. It is safe to perform pleural drainage even though anticoagulation therapy and glucocorticoids are widely used. Chest tubes rather than CVCs are recommended.

Clinical recommendations on lung cancer management during the COVID-19 pandemic.

Coronavirus disease 2019 (COVID-19) is spreading worldwide, and has been declared as an international public health concern. Patients with lung cancer are highly susceptible to infection compared to healthy individuals because of systemic immunosuppression induced by malignancy and anticancer therapy. Furthermore, patients with cancer demonstrate poorer outcomes following infection. Hence, patients with lung cancer should be considered a priority group for COVID-19 prevention. Furthermore, the routine treatment of patients with cancer has been affected during the COVID-19 pandemic, and patients may not have been able to undergo timely and effective antitumor treatment, thereby indicating a poor prognosis. Here, we provide some suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer who have fever and respiratory symptoms. Our medical team also provide clinical recommendations on lung cancer management during the COVID-19 pandemic, for carrying out meticulous and individualized clinical management of lung cancer patients and maximum protection to effectively prevent COVID-19. KEY POINTS: Significant findings of the study This article provides suggestions for early identification of COVID-19 and differential diagnosis in patients with lung cancer with fever and respiratory symptoms. What this study adds This article makes clinical recommendations on lung cancer management during the COVID-19 pandemic.

Characteristics of pediatric SARS-CoV-2 infection and potential evidence for persistent fecal viral shedding.

We report epidemiological and clinical investigations on ten pediatric SARS-CoV-2 infection cases confirmed by real-time reverse transcription PCR assay of SARS-CoV-2 RNA. Symptoms in these cases were nonspecific and no children required respiratory support or intensive care. Chest X-rays lacked definite signs of pneumonia, a defining feature of the infection in adult cases. Notably, eight children persistently tested positive on rectal swabs even after nasopharyngeal testing was negative, raising the possibility of fecal-oral transmission.

[Clinical Management of Lung Cancer Patients during the Outbreak of 2019 Novel Coronavirus Disease (COVID-19)].

Since late December 2019, an outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. With the spread of COVID-19, the routine clinical diagnosis and treatment for lung cancer patients has been disturbed. Due to the systemic immunosuppressive of lung cancer patients caused by the malignancy and anticancer treatments, lung cancer patients are more susceptible to infection than healthy individuals. Furthermore, patients with cancer had poorer prognosis from infection. Lung cancer patients should be the priority group for COVID-19 prevention. The protection provisions and control measures aiming to protect lung cancer patients from COVID-19 have been increasingly concerned. During the COVID-19 outbreak period, it should be carefully differentiated for fever and respiratory symptoms for lung cancer patients receiving anti-tumor treatment, in order to evaluate the risk of COVID-19. Moreover, it is necessary to carry out meticulous and individualized clinical management for lung cancer patients to effectively protect the patients from COVID-19.